INTRODUCTION Okay, this is going to be as easy at it gets. There are a few other synths out there which appear to have more "detailed" instructions to them, but they are still nothing approaching a "cookbook" and they leave off important information and when you get right down to it are still much more difficult. While there aren't any "detailed" instructions for this synthetic route, all of the synthesis routes to make d-LSD will probably require the equivalent of a Batchelor's degree (4-year college) in chemistry anyway. There are no "easy" synths of LSD. TANSTAAFL. WARNING: This synthesis is almost certainly hazardous to your heath and safety. The mere possession of precursors and chemicals may get you into legal trouble (e.g. POCl3 is used to create nerve gas and export is controlled). The chemicals themselves are toxic. The synthesis is dangerous (e.g. adding POCl3 too fast and generating too much heat). The usual disclaimers apply, including a warning that while nothing inaccurate has been intentionally introduced into this file, there are no guarantees against typos, etc -- you are expected to familiarize yourself with the primary literature if you're actually psychotic enough to try to make this... PRECURSOR MATERIAL A source of lysergic acid is required. Most LSD is probably synthesized from 'diverted' sources of ergotamine or ergonovine (lysergic acid propanolaminde), both of which are used medically or in veterinary med. Bromocriptine is also a novel possible starting material. Other possibilities in this vein might include ergocristine, ergocryptine, ergosine, or ergocornine. Hydergine is another possible source, although the 9,10 double bond would need to be synthesized. There are also plant sources of lysergic acid amides, including morning glories (_ipomea violacea_ and other members of _convolvulaceae_), hawaiian baby woodrose (_argyreia nervosa_), and ergot fungus (_claviceps purpurea_). It is unlikely that anyone actually uses c. pupurea as starting material for LSD synthesis. Most likely diverted ergotamine or ergonovine is used by hydrolizing it to give lysergic acid. HBWR or MG seeds would probably be used before attempting c. pupurea cultivation. SYNTHESIS of d-LSD maleate or tartrate from lysergic acid with POCl3 Primary Ref: Johnson, Ary, Teiger, Kassel. "Emetic Activity of Reduced Lysergamides." Journal of Medicinal Chemistry. 16(5):532-537. 1973. Related: Huang, Marona-Lewicka, Pfaff, Nichols. "Drug Discrimination and Receptor Binding Studies of N-Isopropyl Lysergamide Derivates." Pharmacology, Biochmistry and Behavior. 47(3):667-673, 1994. Oberlender, Pfaff, Johnson, Huang, Nichols. "Stereoselective LSD-like Activity in d-Lysergic Acid Amides of (R)- and (S)-2-Aminobutane." Journal of Medicinal Chemistry. 35(2):203-211, 1992. Hoffman-AJ, Nichols. "Synthesis and LSD-like Descriminative Stimulus Properties in a Series of N(6)-alkyl Norlysergic Acid N,N-Diethylamide Derivates." Journal of Medicinal Chemistry. 28:1252-1255, 1985. NOTE: JMC 35(2):203-211 has some amazing stereoviews of LSD which might interest non-chemists who like to cross their eyes... Under reduced light (or red light) a stirred solution of 3.15g (11 mmol) of d-lysergic acid monohydrate and 7.23g (99 mmol) of diethylamine in 150ml of CHCl3 was brought to reflux by heating. Heat was removed, and 2ml (3.4g, 22mmol) of phosphorous oxychloride (POCl3) was added over a 2 minute period at a rate just sufficient to maintain reflux, being careful not to exceed this rate. The mixture was then refluxed for an additional 4-5 mins until an amber-colored solution resulted. The solution was brought to room temperature and was washed with 200ml of 1M NH4OH. The CHCl3 solution was dried (MgSO4), filtered, and concentrated under vacuum (not allowing the solution to exceed 40 degrees C). The last traces of the solvent were removed at 2-5 mm. The viscious residue was dissolved in a minimum amount of MeOH and acidified with a freshly prepared 20% solution of maleic acid in MeOH. Crystallization occured spontaneously. The needles were filtered, washed with cold MeOH and air-dried. Yield was 66% after further purification by column chromatography over alumina (Brockman) and elution with 3:1 benzene-chloroform. The chromatography takes appx 8-9 hours. Alternatively, it can be crystallized as the (+)-tartrate from MeOH. After crystallizing from cold MeOH, it is diluted with ethyl acetate, filtered and the the crystals are washed with ethyl acetate. This procedure also works for primary amines and small dialkyl amines. LSD, however, probably remains the most worthwhile product. Other interesting amines might be the N-ethyl-N-propyl derivative (LEP) and the morpholide (LSM-775). 75ug of the morpholide have been reported to have been as effective as 50ug of d-LSD but with 45 min onset (vs 1 hour) and a 1 hour peak (vs 4 hours). The procedure would probably work well for LEP, but yields would be reduced for the morpholide. Other N(20)-alkyl-lysergic acid derivatives tend to be more than 10 times less potent than LSD if not effectively inactive. N(1)-acetyl-LSD (ALD-52) is equimolar potent with LSD (90% as potent as LSD by weight) and can be obtained by acetic anhydride acetylation of lysergic acid, followed by preparation of the diethylamide (or vice versa). N(1)-methyl-LSD (MLD) is also roughly as potent as LSD. But for both of these the synthesis introduces needless complications, lower yields and no benefit either pharmacologically or legally -- although for some reason ALD-52 still apparently makes an appearance on the market from time to time. N(6)-ethyl- (and -allyl- and -propyl-) derivates of LSD may be more active than LSD itself, but synthetic routes to these chemicals presently start with LSD and yields would probably inhibit their appearance on the illicit market. (N(6) is the other nitrogen on the ring structure in addition to the N(1) pyrrole/indole nitrogen). Derivatives of LSD (besides LSA/LA-111 and lysergic acid) are not scheduled, but would be prosecutable in the USA under the designer drugs act after testimony from a DEA agent that _in their opinion_ the defendant was planning to distribute them. Now, as "The Mysterious Mister Magneto" posted to alt.drugs.psychedelics, "for shits and giggles," here's the synthesis of N(6)-allyl-LSD from Hoffman and Nichols, 1985 (good luck!!! -- and beware of typos!): (9) 323 mg (1 mM) of LSD was dissolved in 10 ml of chloroform. This was diluted with 70 ml reagent carbon tetrachloride and was added, over 1h, to a refluxing solution of 440 mg (4.15 mM) of BrCN in 30 ml of CCl4. The reaction wa stirred under a nitrogen atmosphere with external heat provided by an oil bath held at 110 C. After the addition was complete, reflux was continued for 6 h. The mixture was allowed to cool and was washed once with 30 ml of 1% aqueous tartaric acid. Following concentration of the organic solution by rotary vacuum evaporation, the residue was partitioned between dichloromethane (2 x 35 ml) and 50 ml of 1% tartaric acid solution. The organic layer was dried in the dark over anhydrous sodium sulfate. Filtration and solvent removal afforded a purple residue that was passed over 5 g of neutral alumina and eluted with 9:1 chloroform-methanol. This crude material was then purified by centrifugal chromatography (chromatotron) using 2-mm plate of neutral alumina (Merck 1092) and elution with dichloromethane. An ammonia atmosphere was maintained by bubbling nitrogen gas through concentrated ammonium hydroxide and continuously purging the chromatotron chamber. The use of silica gel for this purification gave a blue product and a lower overall recovery. The product band eluted from the plate was concentrated under vacuum in the dark and was recrystallized from ethyl acetate or 2-propanol: yield 237 mg (71%); mp 190-191 C (i-PrOH) (8) A mixture of 334 mg (1mM) of (9), 3.0 ml of glacial acetic acid, 0.6 ml of water, and 0.60 g of powdered zinc was stirred together under a nitrogen atmosphere for 4 h, with external heating provided by an oil bath held at 130 C. The reaction flask was then placed in an ice bath, and 3 ml of water an a sufficient quantity of concentrated ammonium hydroxide were added to make the contents strongly alkaline. The basic suspension was extracted with 5 x 10 ml of dichloromethane. The combined organic extract was then dried (Na2SO4), filtered, reduced by rotary evaporation, and dried under high vacuum to yield 295 mg of a tan solid that was one major spot by TLC (silica; 8:2) chloroform-methanol). Purification by centrifugal chromatography over alumina, elution with 9:1 chloroform-methanol under ammonia vapor, and concentration of the eluate band gave a solid that was recrystallized from ethyl acetate-hexanes to yield 190 mg (61%) of tan crystals, mp 196-198 C. (6) A mixture of 66 mg of (8) (0.21 mmol), 48 mg of anhydrous potassium carbonate (0.35 mmol), and allyl bromide (0.24 mmol) in 2 ml of freshly distilled DMF in a small amber vial was stirred under N2 at room temperature. The reaction was monitored by TLC (silica; 9:1 CHCl3-MeOH) at 1-h intervals to determine reaction completion. When the starting material (8) had been consumed, the solvent was stripped from the reaction under high vacuum. The resulting residue was extracted with chloroform (5 x 5ml), dried (Na2SO4), and reduced by rotary evaporation to yield the product, usually as a white solid. Centrifugal chromatography over a 1-mm alumina plate and elution with methylene chloride under ammonia atmosphere led to the separation of two blue, highly fluorescent fast-moving bands. The first band eluted from the plate was the major component and was concentrated, dissolved in a minimum of hot benzene, filtered, and cooled. Hexane was added when necessary to induce crystallization to yield 67 mg (88%) of N(6)-allyl LSD mp 88-90 C Now, do the math on the yields. If you don't screw anything up the final yield is 38% of the d-LSD that you started with, for roughly the same gain in potency, or less.